Developing Asymmetric Gold Redox Catalysis for Challenging Chemical Transformations

项目摘要/摘要 拟议项目的目标是开发有机合成方法，用于潜在的应用 生物化学和医药科学解决重大问题(优化原料药生产工艺和 为铅化合物的制备提供新的方法等)，最终可能有益于人类健康。 该项目研究团队之前的工作重点是开发新的过渡金属催化剂 具有挑战性的化学转化的应用，以达到各种不同的有效合成 用于医学和生物研究的化学品。最近，由于使用了强氧化剂或 实现了光活化条件下，金(I)氧化为金(III)，尽管固有的高度氧化 潜力。这些发现进一步推动了金催化领域的发展，使氧化还原化学成为 进入催化循环的替代路径。然而，目前的金催化体系存在主要障碍。 这限制了它在促进一些典型的化学合成方面的全部效用，例如在 氧化还原化学，在不需要快速脱胶的情况下获得乙烯基金中间体，以及金的整合. 酸与氧化还原化学的反应性等。拟议的项目将通过开发 新的策略和催化剂，并通过提供新的医学上重要的途径来获得 通常很难访问。该项目的目标将解决黄金催化中的两个基本问题： 1)能否通过以金(I)为载体的手性配体调控来实现不对称金氧化还原催化 州政府？以及2)多种金催化反应模式(对酸、乙烯基金和氧化还原)的整合 化学)在一个周期内集成，以实现具有良好立体选择性的高效转化。 我们的研究计划将集中在以下四个具体方向：1)开发新的氧化 实现金氧化的条件为更广泛的底物用于金氧化还原催化； 金/铁双催化体系获得乙烯基金直接构筑C-C和C-X键的反应活性 大环化合物的合成；3)应用手性N，P配体实现对映体选择性的双烯烃合成。 功能化以提供可能影响不对称金氧化还原催化的关键因素；以及4) 开发新型三氮唑类手性配体体系实现金(III)的不对称催化 立体选择性的C-C和C-X键结构。这项研究的预期结果将导致新的 生物医学上重要分子和新分子的替代途径的策略和方法 作为分子探针或潜在的治疗方案的积木。

Project Summary/Abstract The proposed project’s goal is to develop organic synthesis methodologies for potential applications in biochemistry and medicinal science to solve important problems (optimizing API production process and providing new methods for lead compound preparation etc.), which could ultimately benefit human health. Previous work by this project’s research team has focused on developing new transition metal catalysts with applications for challenging chemical transformation to reach an efficient synthesis of diverse chemicals for medicinal and biological research. Recently, with the employment of strong oxidants or photoactivation conditions, gold(I) oxidation to gold(III) were realized, despite the intrinsic high oxidation potential. These discoveries further advanced the field of gold catalysis, adding redox chemistry as an alternative path into the catalytic cycle. However, major hurdles in the current gold catalytic system exist that limit its full utility to promote some typical chemical synthesis such as asymmetric transformations in redox chemistry, accessing vinyl-gold intermediate without rapid protodeauration, and integration of gold p- acid reactivity with redox chemistry, etc. The proposed project will address these hurdles by developing new strategies and catalysts and by providing new medicinally important avenues toward structures which are often difficult to access. The project aim will address two fundamental questions in the gold catalysis: 1) Can asymmetric gold redox catalysis be achieved through chiral ligand control with gold(I) as the resting state? and 2) Will the integration of multiple gold catalysis reaction modes (p-acid, vinyl-gold and redox chemistry) be integrated in one cycle to achieve highly efficient transformations with good stereoselectivity. Our research program will focus on the following four specific directions: 1) developing new oxidation conditions to achieve gold oxidation for a broader scope of substrates for gold redox catalysis; 2) applying gold/iron dual catalytic system to access vinyl-gold reactivity for direct C-C and C-X bond construction and macrocyclic compound synthesis; 3) applying chiral N,P ligand to achieve enantioselective alkene di- functionalization to provide the key factors that might influence asymmetric gold redox catalysis; and 4) developing new triazole-based chiral ligands systems to achieve gold(III) asymmetric catalysis for rapid and stereoselective C-C and C-X bond constructions. The research’s expected outcomes will result in new strategies and methods for alternative approaches toward biomedically important molecules and new building blocks as molecular probes or potential therapeutic solution.